Certain strains of mice spontaneously develop thymic T-cell lymphomas at very high frequency within about 1 year of age. The mechanism appears to involve mutagenesis induced by activation or deregulation of one of a number of host genes by nearby insertion into host DNA of sequences of murine leukemia viruses (MuLV), usually of the recombinant mink cell focus-inducing (MCF) class. B cell lymphomas also occur in mice, usually at low incidence and, since they are seen after 1 year of age, are more commonly seen in strains in which T cell lymphoma is not prevalent. Ecotropic (mouse cell-tropic) rather than MCF viruses have been implicated in some B cell lymphoma systems but no general mechanism has been clearly established. NFS.V+ mice (a group of strains in which genes coding for high level expression of infectious ecotropic virus were introduced into a virus negative, very low lymphoma background) develop spontaneous lymphomas of relatively long latency but at high frequency. About 90% are B cell and comprise a broad range of morphological types, including lymphoblastic, small lymphocytic, follicular and marginal zone lymphomas. The great majority of NFS.V+ lymphomas contain one or more new non-germline integrations of ecotropic MuLV, and ecotropic and often MCF viruses can easily be isolated. In genetically closely comparable virus-negative mice lymphoma is not totally absent, but mostly occurs later in life as low grade neoplasms of much lower incidence. This suggests that the role of MuLV in B cell lymphomagenesis may be in accelerating initiation and influencing progression.CFW mice, long considered a low lymphoma strain, have been found to have a high frequency of T and B cell lymphoblastic and B cell follicular lymphomas. We have found that lymphoma development is closely correlated with presence of MuLV. Individual mice may be totally virus-free or may express high levels of ecotropic and often MCF MuLVs and that development of lymphoma is strongly correlated with presence of virus. The CFW population is virologically diverse, both phenotypically and genotypically, so that random selection of animals provides great variation in potential for lymphoma development. - Mice, murine leukemia viruses, somatic integrations, B-cell lymphoma, splenic marginal zone lymphoma.